the steroid catabolic pathway of the intracellular pathogen rhodococcus equi is important for pathogenesis and a target for vaccine development胞内病原体的类固醇异化的途径红球菌属等是重要的发病机理和疫苗开发的目标.pdfVIP

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2017-09-14 发布于上海
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the steroid catabolic pathway of the intracellular pathogen rhodococcus equi is important for pathogenesis and a target for vaccine development胞内病原体的类固醇异化的途径红球菌属等是重要的发病机理和疫苗开发的目标.pdf

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the steroid catabolic pathway of the intracellular pathogen rhodococcus equi is important for pathogenesis and a target for vaccine development胞内病原体的类固醇异化的途径红球菌属等是重要的发病机理和疫苗开发的目标

The Steroid Catabolic Pathway of the Intracellular Pathogen Rhodococcus equi Is Important for Pathogenesis and a Target for Vaccine Development 1 2 1 2 1 R. van der Geize *, A. W. F. Grommen , G. I. Hessels , A. A. C. Jacobs , L. Dijkhuizen 1 Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Microbiology, University of Groningen, Groningen, The Netherlands, 2 Intervet International BV, Microbiological RD, Boxmeer, The Netherlands Abstract Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and immunocompromised animals and humans. Despite its importance, there is currently no effective vaccine against the disease. The actinobacteria R. equi and the human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary diseases. Recently, we have shown that essential steps in the cholesterol catabolic pathway are involved in the pathogenicity of M. tuberculosis. Bioinformatic analysis revealed the presence of a similar cholesterol catabolic gene cluster in R. equi. Orthologs of predicted M. tuberculosis virulence genes located within this cluster, i.e. ipdA (rv3551), ipdB (rv3552), fadA6 and fadE30, were identified in R. equi RE1 and inactivated. The ipdA and ipdB genes of R. equi RE1 appear to constitute the a-subunit and b-subunit, respectively, of a heterodimeric coenzyme A transferase. Mutant strains RE1DipdAB and RE1DfadE30, but not RE1DfadA6, were impaired in growth on the steroid catabolic pathway intermediates 4-androstene-3,17-dione (AD) and 3aa-H-4a(39-propionic acid)-5a- hydroxy-7ab-methylhexahydro-1-indanone (5a-hydroxy-methylhexahydro-1-indanone propionate; 5OH-HIP). Interestingly, RE1DipdAB and RE1DfadE30, but not RE1DfadA6, also displ